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Philip Hampton,1 Emma Borg,2 Jes Birger Hansen,2 Matthias Augustin3 1Department of Dermatology, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK; 2LEO Pharma A/S, Ballerup, Denmark; 3Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, GermanyCorrespondence: Philip HamptonDepartment of Dermatology, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, NE7 7DN, UKEmail philip.hampton@nhs.netPurpose: Both brodalumab and guselkumab improve skin clearance in patients with moderate-to-severe plaque psoriasis after inadequate response to ustekinumab. In the absence of a direct head-to-head comparison, the relative efficacy of brodalumab and guselkumab in non-responders to ustekinumab were compared using a matching-adjusted indirect comparison (MAIC).Patients and Methods: Individual patient data for brodalumab (n = 121) were pooled from the AMAGINE-2 and -3 trials and adjusted using a propensity score reweighting method, so that baseline and week 16 characteristics matched the aggregate published data of patients with an inadequate response to ustekinumab who switched to guselkumab (n = 135) in the NAVIGATE trial.Results: After inadequate response to ustekinumab, brodalumab resulted in significantly higher psoriasis area and severity index (PASI) 90 rates versus guselkumab at post-treatment switch week 12 (62.7% vs 48.1%, relative difference 14.6% [95% confidence interval [CI] 5.3– 23.9], p = 0.002 [number needed to treat [NNT] = 6.8]) and week 36 (63.7% vs 51.1%; relative difference 12.6% [95% CI 4.1– 21.0]; p = 0.004 [NNT = 7.9]) and PASI 100 rate at week 36 (40.3% vs 20.0%; relative difference 20.3% [95% CI 11.8– 28.7]; p < 0.001 [NNT = 4.9]).Conclusion: In this MAIC, brodalumab was associated with greater improvements than guselkumab in inadequate responders to ustekinumab. Switching to brodalumab in such patients may be a more effective strategy than switching to guselkumab.Keywords: brodalumab, guselkumab, psoriasis

Background Psoriasis vulgaris is not easy to manage, even when mild. Knowledge of the efficacy of most topical therapies in this population is limited. Objective To assess the efficacy of calcipotriene 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) foam in patients with mild psoriasis. Methods Post hoc analysis was performed on pooled data for subjects with mild psoriasis at baseline from 2 Phase 3 and 1 Phase 2 clinical trials. All subjects applied Cal/BD foam or vehicle foam once daily for at least 4 weeks. Efficacy assessments included treatment success (defined as IGA=0), mPASI, BSA, and the composite IGAeBSA score. Results Of the 848 subjects, 164 had mild psoriasis at baseline. Within this subpopulation of mild subjects, Cal/BD foam demonstrated significant efficacy over vehicle at week 4 in terms of the proportion of subjects achieving complete clearance of visible lesions (IGA=0). Significant improvements were also observed for mPASI, BSA, and IGAeBSA score. Limitations These post hoc analyses need to be confirmed with prospective studies. Conclusion Once-daily Cal/BD foam for 4 weeks demonstrated effectiveness in treating subjects with mild psoriasis, a population in which demonstration of treatment success can be difficult, because of the requirement for complete clearance of visible disease. Clinicaltrials.gov: NCT02132936, NCT01866163, and NCT01536938 J Drugs Dermatol. 2021;20(8):822-828. doi:10.36849/JDD.5743.

Introduction Clinical trials have shown that psoriasis patients who achieve complete skin clearance are more likely to report no impairment in health-related quality of life (HRQoL) and no psoriasis symptoms versus patients who achieve almost complete skin clearance. However, real-world data are lacking. The objective of this study was to estimate the real-world proportion of moderate-to-severe psoriasis patients on biologic treatment who achieved a Psoriasis Symptom Inventory (PSI) total score of 0 (PSI 0; no symptoms) and a Dermatology Life Quality Index (DLQI) score of 0/1 (DLQI 0/1; no impact on HRQoL), and to study the relationship between patient-reported symptoms and HRQoL versus physician-reported psoriasis severity (Psoriasis Area and Severity Index [PASI]). Methods The PSO-BIO-REAL study was a multinational, prospective, real-world, non-interventional study that included patients aged ≥ 18 years with moderate-to-severe plaque psoriasis who had initiated biologic therapy (either biologic-naïve or had switched biologics [biologic-experienced]). Psoriasis symptoms were evaluated using the PSI, and HRQoL was assessed using the DLQI. Assessments were conducted at baseline and at 6 and 12 months after initiating biologic treatment. Associations between PSI and DLQI with PASI were evaluated using Spearman correlation coefficients. Post-hoc analyses evaluated individual PSI items and the association to PASI response, DLQI and PSI by index biologic. Results At 12 months, 25.5% of patients achieved PSI 0, and 51.2% achieved DLQI 0/1, with greater proportions achieving these scores among biologic-naïve than among biologic-experienced patients. There was a moderate-to-strong correlation between PSI and DLQI scores and PASI scores, with 64.8% of patients with absolute PASI 0 and 19.4% with absolute PASI > 0 ≤ 2 achieving PSI 0 (6 and 12 months pooled). Achievement of response varied by index biologic. Conclusion This study demonstrates that in a real-world setting patients’ QoL improves with skin clearance. The results also demonstrate that the correlation between skin clearance and improvements in HRQoL (DLQI) and psoriasis symptoms (PSI) is not complete, which highlights the importance of considering both patient- and physician-reported outcomes in the assessment of psoriasis treatment outcomes.

Background The product of the Physician Global Assessment and body surface area (PGA×BSA) is simpler to use than the Psoriasis Area and Severity Index (PASI), which lacks sensitivity in patients with mild psoriasis. Objective To compare the PGA×BSA versus the modified PASI (mPASI) for assessing disease severity and therapeutic response to calcipotriol/betamethasone dipropionate (Cal/BD) foam. Methods This post hoc analysis evaluated the efficacy of Cal/BD foam in mild, moderate, and severe psoriasis, as assessed by the PGA×BSA and mPASI, using data from 3 randomized controlled trials ( NCT01536886 , NCT01866163 , NCT02132936 ). Spearman correlation and Bland-Altman plots were used to compare the PGA×BSA with the mPASI. Results Proportions of patients receiving Cal/BD foam achieving 75% response for PGA×BSA and mPASI at weeks 1, 2, and 4 were similar and significantly greater than with vehicle (P ≤ .002 at all timepoints); at week 4, mean improvements were 51.0% and 50.7%, respectively. Spearman correlations for mild, moderate, and severe psoriasis were moderate to high between PGA×BSA and mPASI at baseline (r = .51, .72, and .86, respectively; n = 126, 465, and 58, respectively) and high at week 4 (r = .80, .81, and .89, respectively; n = 121, 452, and 58, respectively) (P Limitations Pooled data from different trials were not prespecified for post hoc analysis. Interrater reliability was not assessed. Conclusion Pooled data analysis showed that the PGA×BSA and mPASI correlation was higher with increasing psoriasis severity.

Introduction Obesity, smoking, and alcohol consumption are prevalent in psoriasis patients and have been associated with increased disease severity and reduced treatment adherence and response. This post hoc analysis of pooled data from the phase 3 AMAGINE-2 and -3 trials compared the efficacy of brodalumab versus ustekinumab in psoriasis patients with aggravating and potentially treatment-confounding lifestyle risk factors. Methods This post hoc analysis evaluated complete skin clearance, as measured by a 100% reduction of Psoriasis Area and Severity Index (PASI100) and quality of life (QoL), as measured by a Dermatology Life Quality Index (DLQI) score of 0/1, by the presence of risk factors (obesity, tobacco or alcohol use). A competing risk model assessed cumulative incidence over 52 weeks with outcomes of PASI100 or inadequate response. Results This analysis included 929 patients (brodalumab 210 mg, n = 339; ustekinumab, n = 590) with moderate-to-severe psoriasis. At week 52, odds ratios (95% confidence intervals [CIs]) for complete clearance with brodalumab versus ustekinumab were 2.50 (1.14–5.46, P = 0.0186), 4.64 (2.80–7.69, P < 0.0001), 2.06 (1.25–3.40, P = 0.0045), and 2.55 (0.55–11.91, P = 0.2117) in patients with no, one, two, or three risk factors, respectively. Corresponding odds ratios (ORs) (95% CIs) for DLQI 0/1 with brodalumab versus ustekinumab were 1.72 (0.78–3.79, P = 0.1883), 2.49 (1.54–4.02, P

Introduction Biologic treatments for psoriasis are commonly switched. Treatment persistence represents an important parameter related to long-term therapeutic performance. The objective of the study was to analyse the real-world persistence with biologics over time in the treatment of psoriasis. Methods A retrospective observational study of adults with psoriasis was conducted based on Swedish national registry data from 2010 to 2018. Patients included were treated with a biologic between 2010 and 2018. Treatment episodes were identified from the drug’s date of dispensation recorded in the Prescribed Drug Register to the end of supply of the drug. Median persistence was estimated by Kaplan–Meier survival curves for patients who received adalimumab, etanercept, secukinumab, ustekinumab and ixekizumab. Descriptive analysis of change in persistence over time for 3-year running cohorts was also carried out. Results A total of 2292 patients were analysed. Patients who received ustekinumab had the longest median persistence [49.3 months, 95% confidence interval (CI) 38.0–59.1] and etanercept the shortest (16.3 months, 95% CI 14.5–19.0). Median persistence was longer in biologic-naive than biologic-exposed patients. Persistence for ustekinumab decreased by almost 50% over the study period, from a median of 62.3 (95% CI 45.6–∞) months in 2010–2011 to 32.7 (21.2–49.3) months in 2014–2016. Conclusions Persistence with biologics was, on average, relatively low, given the chronic nature of psoriasis. Changes in persistence over time seemed to be attributable to changes in the therapeutic landscape, providing patients with more options to switch biologic treatments if their current management was considered suboptimal. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00616-7.

Background: Real-world data for actinic keratosis treatment in the United States is lacking. Objectives: To understand real-world treatment patterns for actinic keratosis by type and modality, and compare effectiveness and safety of therapies, either alone or in combination. Methods: Medical charts of 429 patients were identified; clinical and outcome data were analyzed. Results: The first treatment after the index diagnosis was most frequently a procedure, followed by a topical agent. Treatment with 5-fluorouracil, ingenol mebutate, imiquimod, cryotherapy, or cryotherapy plus one topical (CRYO+One Topical) reduced actinic keratoses by 66.0%, 69.3%, 72.5%, 72.9%, and 73.0%, respectively; ≥75% clearance (AKCLEAR 75) was achieved in 57.1%, 72.7%, 57.1%, 62.4%, and 62.0% of those patients. Treatment effectiveness was positively correlated with the number of baseline actinic keratoses for topical and for procedural plus topical combination treatments, but not for procedural treatments alone. Adverse reactions (ARs) were more common with cryotherapy (9.7%); local skin responses (LSRs) were more common with field-directed (18.5%-43.1%) and CRYO+One Topical therapy (21.3%). Limitations: This was a retrospective study of limited duration and population size. Conclusions: The most commonly used treatments for patients with 6 or more actinic keratoses were topicals and a procedure plus topical combination, which also achieved higher rates of complete clearance than a procedure alone. ARs and LSRs were few in frequency and type.

BACKGROUND: There are a variety of treatment options currently available for plaque psoriasis affecting the scalp, yet scalp psoriasis remains one of the most frustrating and difficult-to-manage forms of the disease. OBJECTIVE: We investigated the efficacy of fixed-combination calcipotriene 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) foam for the treatment of scalp psoriasis. METHODS: Additional (including post-hoc) analysis was conducted on data from a Phase II, randomized, double-blind, multicenter study of Cal/BD foam for the treatment of psoriasis vulgaris (NCT01536938). A total of 302 patients, ages 18 years or older, with psoriasis vulgaris of at least mild severity (scalp involvement of at least 10%) were included; 100, 101, and 101 patients were randomized to once-daily Cal/BD foam, Cal foam, or BD foam, respectively. Assessments included a severity score for lesion redness, scaliness, and plaque thickness, modified Psoriasis Area and Severity Index (mPASI) score, proportion of patients with reduction of 50 percent or greater in total sign score (TSS-50), and proportion of patients with at least a 75-percent reduction in mPASI score (mPASI-75). RESULTS: Patients achieved greater improvements in their scalp psoriasis with Cal/BD foam versus BD or Cal foam alone at Week 4 considering mPASI, mPASI-75, and TSS-50 outcomes. After four weeks of treatment, more patients receiving Cal/BD foam had a severity score for redness, scaliness, and thickness indicating “none” or “mild” versus BD foam or Cal foam alone. Improvements on the scalp appear to be consistent with those on the trunk and limbs. CONCLUSION: Scalp lesion severity improved considerably and rapidly with a four-week regimen of Cal/BD foam, suggesting that Cal/BD foam is an effective topical treatment option for scalp psoriasis.

Background: The fixed-dose combination foam formulation of calcipotriene 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) has demonstrated efficacy and a favorable safety profile for the treatment of plaque psoriasis. Recently, a topical lotion of the combination of halobetasol 0.01% plus tazarotene 0.045% (HP/TAZ) was approved for treating adult plaque psoriasis. Currently, no head-to-head studies have compared Cal/BD foam with HP/TAZ lotion. Objective: Compare the effectiveness and drug incremental cost per responder (ICPR) of Cal/BD foam vs. HP/TAZ lotion in moderate-to-severe plaque psoriasis. Methods: An anchor-based, matching-adjusted indirect comparison was conducted for PGA treatment success (Physician’s Global Assessment of “clear” or “almost clear,” [PGA 0/1] with at least a 2-point improvement) using individual patient data from 3 randomized clinical studies of Cal/BD foam and published data from 2 randomized, Phase 3 clinical studies of HP/TAZ lotion. The number needed to treat and ICPR were also calculated. Results: After reweighting of patients in the Cal/BD foam studies to match summary baseline characteristics of the HP/TAZ lotion study patients and anchoring to vehicle effect, 4 weeks of Cal/BD foam produced a significantly greater rate of treatment success than 8 weeks of HP/TAZ lotion treatment (51.4 vs. 30.7%; treatment difference = 20.7%, p Conclusions: The indirect comparison analyses showed that Cal/BD foam was associated with a greater rate of treatment success, lower ICPR, and quicker treatment response than HP/TAZ lotion in adult patients with moderate-to-severe plaque psoriasis.

Introduction Dans les etudes AMAGINE 2/3, le brodalumab est associe a un blanchiment total et a une amelioration de la qualite de vie chez les patients atteints d’un psoriasis en plaques modere a severe. L’objectif de l’analyse post-hoc (AMAGINE 2/3) est de comparer l’impact du brodalumab et de l’ustekinumab sur la qualite de vie et les symptomes, a l’aide du DLQI et du PSI, dans deux populations de patients psoriasiques avec ou sans rhumatisme psoriasique. Materiel et methodes L’analyse a ete realisee a partir des donnees de l’etude AMAGINE 2/3 des patients traites par brodalumab 210 mg (bimensuel) ou ustekinumab 45–90 mg (a J1, S4, S16, S28 et S40, jusqu’a S52). La comparaison des deux traitements des patients avec un DLQI 0/1 et une reponse PSI (PSI = 8 et 0 item > 1) dans les deux populations a ete realisee via un test Cochran-Mantel-Haenszel ajuste. Le benefice clinique cumule pour chaque critere a ete determine par l’aire sous la courbe (ASC) sur 52 sem et 24 sem (DLQI et PSI). Resultats Le pourcentage de patients avec un RP, groupe ‘PSO_RP’ etait de 23 % (brodalumab) vs 18 % (ustekinumab). Quel que soit le traitement, les patients ‘PSO_RP’avaient plus d’antecedents de biotherapies compares aux patients ‘PSO seul’. A S12 et S52, dans les groupes ‘PSO_RP’ et ‘PSO seul’, le pourcentage de patients avec un DLQI 0/1 etait significativement plus eleve dans le groupe traite par brodalumab que par ustekinumab (‘PSO-RP’ S12 : 61 % vs 46 %, S52 : 49 % vs 33 % ; ‘PSO seul’ S12 : 60 % vs 45 %, S52 : 56 % vs 41 %). Dans les groupes ‘PSO_RP’et ‘PSO seul’, le pourcentage de patients repondeurs PSI etait significativement plus eleve dans le groupe traite par brodalumab que par ustekinumab (‘PSO_RP’ a S12 : 61 % vs 45 %, S52 : 43 % vs 25 % seul'S12 : 67 % vs 49 %, S52 : 58 % vs 42 %). Le benefice cumule sur 52 semaines pour le DLQI 0/1 etait significativement plus important avec le brodalumab qu’avec l’ustekinumab dans les groupes ‘PSO_RP’ et ‘PSO seul’. Pour les patients ‘PSO_RP’ les ASC moyenne et normalisee correspondantes etaient plus elevees avec le brodalumab qu’avec l’ustekinumab (2630 (51 %) et 1873 (36 %)). Chez les patients ‘PSO seul’, ces valeurs etaient de 2 798 (54 %) pour le brodalumab contre 2107 (41 %) pour l’ustekinumab. Le benefice cumule sur 24 semaines pour la reponse PSI etait significativement plus important avec le brodalumab qu’avec l’ustekinumab dans les groupes ‘PSO_RP’ et ‘PSO seul’. Une correlation a ete evoquee entre l’obtention d’un DLQI 0/1 et la reponse PASI chez les patients avec ou sans RP, suggerant que la qualite de vie est dependante de la reponse PASI. La qualite de vie s’ameliore avec l’importance du blanchiment des lesions. Discussion L’analyse post-hoc des etudes AMAGINE2/3 montre que le traitement par brodalumab 210 mg est associe a de plus grandes ameliorations de la qualite de vie que l’ustekinumab, et ce independamment du RP.

Dear Editor, Thank you for the opportunity to respond to Dr. Glick and colleagues regarding their Letter to the Editor and for allowing us to provide clarity on aspects of the methodology in our re...

Introduction Venous thromboembolism (VTE) frequently complicates the course of active cancer with a significant impact on morbidity and mortality. The results of CATCH trial for treatment of cancer-associated thrombosis (CAT) have been reported and included patients with and without metastatic disease. As metastatic disease is known to be associated with a higher risk of recurrent VTE and bleeding, we performed these post hoc analyses to assess the recurrent VTE (rVTE), recurrent deep vein thrombosis (rDVT), and bleeding events (major bleeding (MB), clinically relevant (CRB) and clinically relevant non-major (CRNMB)) in patients with CAT with metastatic disease. Risk factors associated with rVTE, rDVT and CRB were also explored. Method CATCH (ClinicalTrials.govNCT01130025; Lee A et al. JAMA 2015) was a Phase III, multinational, randomized, active-controlled, open-label trial. Patients with solid tumor cancer and haematological malignancies were included. Patients were randomized to receive therapeutic dosing of tinzaparin (175 U/kg OD) vs warfarin (INR target 2.0 - 3.0). Treatment was given for up to 6 months. The primary efficacy outcome was the composite of symptomatic DVT, symptomatic nonfatal pulmonary embolism (PE), fatal PE, incidental proximal DVT and incidental proximal PE. All cumulative incidence VTE and MB outcome were objectively documented and centrally adjudicated in a treatment-blinded fashion. Patients who had known metastatic solid tumor at presentation were included in these analysis. The regression model compared the two treatment groups adjusting for competing risks and geographical region and history of VTE. Results Among the CATCH study population, 55% had metastatic disease. Of these patients, 247 and 245 received tinzaparin and warfarin, respectively, with no significant differences in patient characteristics between treatment groups. Patients with metastatic disease had a higher incidence of rVTE (10.2% vs 7.0%) and symptomatic non-fatal rDVT (5.5% vs 2.9%) compared to patients without metastatic disease. Patients with metastatic disease also had a higher incidence of MB (2.8% vs 1.9%), CRB (17.7%% vs 11.8%) and CRNMB (15.0% vs 10.5%) compared to patients without metastatic disease. rVTE occurred in significantly fewer patients assigned to tinzaparin (6.8%) versus warfarin (14.4%) (HR 0.45; 95%CI 0.25-0.80; p=0.007). rDVT also occurred significantly less frequently in patients assigned to tinzaparin (3.0%) versus warfarin (8.4%) (HR 0.34; 95%CI 0.15-0.81; p=0.015). 96% of rVTE were symptomatic. There was no significant difference in MB between tinzaparin- and warfarin-treated patients (4.0% vs 1.6%; HR 2.17; 95%CI 0.71-6.65; p=0.177), but tinzaparin was associated with significantly lower risk of CRB (15.8% vs 19.6%; HR 0.63; 95%CI 0.41-0.97; p=0.037) and CRNMB (12.1% vs 18.0%; HR 0.53; 95%CI 0.33-0.84; p=0.008). Factors associated with rVTE in patients with metastatic disease included central venous catheterization (HR 0.10; 95%CI 0.01-0.79; p=0.029), venous compression from mass or adenopathy (HR 3.99; 95%CI 2.14-7.43; p 75 (HR 2.56; 95%CI 1.43-4.60; p=0.002) and known intracranial pathology (HR 2.24; 95%CI 1.07-4.66; p=0.031) were found to be significant risk factors for CRB. Conclusion CAT patients with metastatic diseases have higher risks of rVTE and bleeding compared with patients without metastases. Amongst CAT patients with metastatic solid tumors, treatment with tinzaparin was associated with significantly lower risk of rVTE and rDVT and significantly lower risk of CRB and CRNMB compared with warfarin. Tinzaparin offers a favourable risk-benefit profile in treatment of CAT in patients with metastatic solid tumors. Disclosures Lee: Pfizer: Consultancy, Honoraria; BMS: Research Funding; LEO Pharma A/S: Consultancy, Honoraria; Bayer: Consultancy, Honoraria, Other: Advisory board, steering committee. Bauersachs:Aspen: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; LEO Pharma A/S: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Turpin:LEO Pharma Canada: Current Employment. Hansen:LEO Pharma A/S: Current Employment. Khorana:Leo Pharma: Honoraria; Merck: Research Funding; Array: Other: Research funding (to institution); Leap: Research Funding; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Pharmacyclics: Honoraria; Janssen: Honoraria; Pfizer: Honoraria; Medscape: Honoraria; Bayer: Honoraria; BMS: Honoraria, Research Funding; Sanofi: Honoraria.

Background: It is unclear if there are any distinct AK patient populations that might respond best to a given treatment. Objective: To identify if a distinct subgroup of patients with AK might respond better to treatment with ingenol mebutate (IngMeb) versus diclofenac sodium (DS). Methods: Complete clearance of AK and mean lesion reduction at end of first treatment course and week 17 were evaluated within subgroups. Results: 502 patients (255 IngMeb; 247 DS) were included in the analysis. At week 17, complete clearance was achieved by more patients treated with IngMeb versus DS within the majority of patient subgroups, including patients with

Introduction Le rhumatisme psoriasique peut toucher entre 20 et 40 % des patients atteints de psoriasis. L’objectif de l’analyse post hoc des etudes AMAGINE 2/3 est de comparer les traitements brodalumab vs ustekinumab dans l’obtention d’une reponse PASI 100 dans deux populations de patients atteints de psoriasis en plaques modere a severe avec ou sans rhumatisme psoriasique (RP). Materiel et methodes L’analyse a ete realisee a partir des donnees de setudes AMAGINE 2/3 des patients traites par brodalumab 210 mg (bimensuel) ou ustekinumab 45–90 mg (a j1, S4, S16, S28 et S40, jusqu’a S52). Les analyses statistiques ont ete faites via la methode Cochran–Mantel–Haenszel ajustee et par un modele de risque competitif pour l’incidence cumulee du blanchiment total sur 52 sem. (PASI 100, reponse inadequate sPGA ≥ 3 ou sPGA = 2 sur ≥ 4 sem. ou apres 16 sem.). Le benefice clinique cumule pour le PASI 100 a ete determine par l’aire sous la courbe (ASC) sur 52. Resultats A S12 et S52 dans les deux groupes « PSO_RP » et « PSO seul », le pourcentage de patients ayant une reponse PASI 100 etait significativement plus eleve dans le groupe traite par brodalumab (vs ustekinumab). Quel que soit le traitement, les patients « PSO_RP » avaient davantage d’antecedents de biotherapies que les patients « PSO seul ». L’analyse par le modele de risques competitifs a montre que le pourcentage de patients « PSO_RP » atteignant une reponse PASI etait significativement plus important avec le brodalumab qu’avec l’ustekinumab (41 % vs 16 %). Le temps median pour obtenir un blanchiment complet etait de 15 semaines pour le brodalumab (pour ustekinumab : non determine). Chez les patients « PSO seul », la reponse PASI 100 etait atteinte chez plus de patients traites par brodalumab que par ustekinumab (77 % vs 53 %). Le temps median pour obtenir un blanchiment complet etait de 13 et 36 semaines pour brodalumab et ustekinumab, respectivement. Le benefice cumule sur 52 semaines pour la reponse PASI 100 etait significativement plus important avec le brodalumab qu’avec l’ustekinumab dans les deux sous-groupes « PSO_RP » et « PSO seul ». Pour les patients « PSO_RP », ASC moyenne et normalisee correspondantes etaient plus importantes avec le brodalumab qu’avec l’ustekinumab (2027 [39 %] vs 1100 [21 %]). Chez les patients « PSO seul », ces valeurs etaient de 2319 (45 %) pour le brodalumab contre 1385 (27 %) pour l’ustekinumab. Il a ete observe sur 52 semaines une augmentation graduelle de la reponse PASI plus importante pour le brodalumab que pour l’ustekinumab (84 % vs 68 %) chez les patients avec et sans RP. Discussion Dans les etudes AMAGINE2/3, il a ete montre une plus grande proportion de patients ayant un blanchiment complet avec le brodalumab qu’avec l’ustekinumab. Cette analyse confirme une efficacite plus importante du brodalumab chez le patient psoriasique avec ou sans RP.

not available.

Background Plaque psoriasis has significant impact on patients’ quality of life. Topical therapy is considered the treatment mainstay for mild‐to‐moderate disease according to guidelines. Calcipotriol/betamethasone dipropionate (Cal/BD) [0.005%/0.05%] aerosol foam is indicated for psoriasis vulgaris treatment in adults. Cal/BD foam trials demonstrated improved efficacy and similar safety in this population. Psoriasis treatment is complicated by the broad range of disease presentation, variability and therapeutic options; particularly decisions on transition from topical to non‐biologic systemic treatment are difficult. Assessing comparative effectiveness of treatment options provides meaningful value to treatment decisions. Objective To compare efficacy of Cal/BD foam individual patient data from pooled trials with efficacy of non‐biologic systemic treatments based on aggregated patient characteristics and treatment outcomes. Methods Individual data from four Cal/BD foam trials in 749 psoriasis patients were pooled to conduct matching‐adjusted indirect comparisons. Literature review identified non‐biologic systemic treatment trials where methods, populations and outcomes align with Cal/BD foam trials. Of 3090 screened publications, four studies of apremilast, methotrexate, acitretin or fumaric acid esters (FAE) were included. Results After baseline matching, patients treated with 4 weeks of Cal/BD foam had greater Physician's Global Assessment 0/1 response compared to those treated with 16 weeks of apremilast (52.7% vs. 30.4%; P

not available. Disclosures: Study sponsored by LEO Pharma. Copyright 2018 SKIN

Several pathophysiologic mechanisms have been proposed to explain slow-healing leg ulcers, but little is known about the growth behavior of cells in these wounds. Platelet-derived growth factor-BB applied topically to chronic wounds has shown beneficial effects, although the effects have been less pronounced than would have been expected based on studies on acute wounds. The objective of this study was to compare fibroblasts in culture obtained from chronic wounds (non-healing chronic venous leg ulcers), acute wounds and normal dermis regarding growth, mitogenic response to platelet-derived growth factor-BB and levels of platelet-derived growth factor α-receptor and β-receptor. Fibroblasts were obtained by an explant technique and expanded in vitro using fibroblast growth medium supplemented with 10% fetal bovine serum and used for the assays at their third passage. Growth of chronic wound fibroblasts (n = 8) was significantly (p < 0.05) decreased compared with those from acute wounds (n = 10) and normal dermis (n = 5). Fibroblasts from ulcers older than 3 y grew significantly (p < 0.01) slower than those from ulcers that had been present for less than 3 y. Morphology and size of fibroblasts from the oldest chronic wounds deviated substantially from those of acute wounds and normal dermis, and resembled in vitro aged or senescent fibroblasts. Mitogenic response of chronic wound fibroblasts to human recombinant platelet-derived growth factor-BB was also reduced with ulcer age. No significant differences were found in the amount of either platelet-derived growth factor α-receptor or β-receptor among the three groups. The features decreased growth related to ulcer age, altered morphology, and reduced response to platelet-derived growth factor, indicating that fibroblasts in some chronic wounds have approached or even reached the end of their lifespan (phase III). This might provide one explanation for the non-healing state and therapy resistance to topical platelet-derived growth factor-BB of some venous leg ulcers.

Early initiation of insulin therapy has widely been associated with numerous benefits, including improved glycaemic control and reduced long-term risk of developing microvascular diseases. Biphasic insulins offer a convenient option for insulin initiation, addressing both basal and postprandial insulin requirements with one injection, making them relatively simple for patients to dose. Development of biphasic insulin aspart (BIAsp) has further offered improved postprandial glycaemic control and lower rates of nocturnal and major hypoglycaemia than biphasic human insulin.The safety and efficacy of the 30/70 rapid-acting/intermediate-acting formulation of BIAsp (BIAsp 30) in patients with type 2 diabetes was examined in the IMPROVE study, a 26-week, international, observational trial. In this subanalysis, baseline clinical factors that predicted treatment success, defined as HbA1c7% (53 mmol/mol) without experiencing hypoglycaemia after 26 weeks on BIAsp 30 therapy, were assessed.The composite endpoint was defined for 44,010 (77%) patients from the total cohort of 57,478, and 28,696 of these were included in the statistical examination. The results of the analysis suggest that those with lower baseline HbA1c of ≤8% (≤64 mmol/mol), shorter duration of diabetes at baseline (5 years) and no incidence of major hypoglycaemia at 13 weeks, or minor hypoglycaemia at 4 weeks, before the beginning of the trial were more likely to achieve treatment success.Lower baseline HbA1c, shorter duration of diabetes and no incidence of hypoglycaemia up to 13 weeks prior to initiation are predictors of achieving HbA1c7% without hypoglycaemia with a BIAsp 30 regimen. These results suggest that it is easier to reach target without hypoglycaemia with BIAsp 30 when prescribed earlier. As this was an observational study, lack of control groups or randomisation, as well as varying clinical practices in study countries, potentially introduced bias.ClinicalTrials.gov NCT00659282.

To evaluate if improvements in the quality of diabetes care in Indian clinics can be obtained by simple self-surveillance PC-based software. Method Nineteen Indian diabetes clinics were introduced to the principles of quality assurance (QA), and to a software program, the Steno Quality Assurance Tool (SQAT). Data was entered for an initial 3 months period. Subsequently data were analyzed by the users, who designed plans to improve indicator status and set goals for the upcoming period. A second data entry period followed after 7–9 months. Results QA data was analyzed from 4487 T2DM patients (baseline) and 4440 (follow-up). The average examination frequency per clinic of the following indicators increased significantly: lipid examination (72–87%) ( p =0.007), foot examination (80–94%) ( p =0.02), HbA1c investigation (59–77%) ( p =0.006), and urine albumin excretion investigation (72–87%) ( p =0.006). Outcome parameters also improved significantly: mean (SD) fasting and post prandial BG reduced from 144(16) to 132(16)mg/dl ( p =0.02) and 212(24)–195(29)mg/dl ( p =0.03), respectively. Systolic BP reduced from 139(6) to 133(4) ( p =0.0008)mmHg and diastolic BP from 83(3) to 81(3)mmHg ( p =0.002). Conclusion Quality of diabetes care can be improved by applying SQAT, a QA self-surveillance software that enables documentation of changes in process and outcome indicators.

The relationship between fasting glucose (FG) variability and nocturnal hypoglycemia was assessed using longitudinal data from PREDICTIVE, the large-scale observational study of insulin detemir. An HbA(1c)-corrected correlation was found between these endpoints, suggesting FG variability can serve as a useful marker for this risk in clinical practice.

Anti-tumor necrosis factor (TNF) therapy is known to decrease disease activity of juvenile idiopathic arthritis (JIA), but its effect on longitudinal growth in relation to puberty is not clear. We studied longitudinal growth in response to etanercept treatment in prepubertal and pubertal patients with JIA.Out of 52 children treated with etanercept, we studied 20 prepubertal and 11 early/midpubertal patients adherent to treatment for at least 1 year. We collected data on growth and glucocorticoid medication and calculated each patient's height standard deviation score (SDS) in relation to the mid-parental height, the change of this value (DeltahSDS) from 1 to 0 and 0 to 1 year of treatment, and the change between the DeltahSDS values to assess growth improvement.In the prepubertal group, the relative height SDS (mean +/- standard error of the mean) was 1.8 +/- 0.2, 2.1 +/- 0.3, and 1.9 +/- 0.3, and in the pubertal group 1.1 +/- 0.4, 1.3 +/- 0.3, and 1.1 +/- 0.3 at 1, 0, and +1 year of treatment, respectively. The DeltahSDS before etanercept was 0.3 +/- 0.1 in prepubertal and 0.2 +/- 0.2 in pubertal patients. Over the first year with etanercept, DeltahSDS was +0.2 +/- 0.1 in prepubertal (p = 0.001 vs before etanercept; paired Student t-test) and +0.2 +/- 0.1 in pubertal patients (p = 0.071). Nevertheless, most prepubertal (17/20) and pubertal (8/11) patients had improved growth (DeltahSDS) in response to etanercept treatment when analyzed individually. The need for intraarticular glucocorticoid injections was negatively correlated to the improved growth (p = 0.001).TNF inhibition with etanercept improved growth in a majority of patients with JIA. Our data demonstrate that growth improvement with etanercept was independent of the pubertal growth spurt.